4
(hetero)aryl fluorides resulted in the desired product formation
Chemistry, Research Corporation for Science Advancement
ACCEPTED MANUSCRIPT
under the optimized conditions (Figure 4, 2D-I see SI for
experimental details). The lower room temperature reactivity of
substrates originating from products 2D and 2E was
circumvented by heating the reaction mixture to 80°C. This
initially afforded 2E in 27% yield, and analysis of the 11B NMR
data suggested the presence of deboronated products, which is
consistent with previous reports of deboronation of oCB in the
presence fluoride.14 To sequester fluoride ions and potentially
prevent cage degradation, we used one equivalent of
isopropoxytrimethylsilane under otherwise identical conditions,
which increased the isolated yield of 2E to 44%. Similar
observations were made with the 2,6-difluoropyridine substrate,
but the yield remained nearly identical even with the addition of
the fluoride scavenger. However, upon changing the solvent from
THF to diethyl ether, the isolated yield for 2F increased to 75%.
We attribute this observation to the likely lower solubility of the
KF byproduct in diethyl ether, thereby decreasing its reactivity
towards deboronation. The present SNAr method also proceeds
with meta-carborane under similar conditions, as exemplified by
the formation of 2G (Figure 4C). We also assessed the viability
of conducting sequential C-vertex heterosubstitutions.
Deprotonation of 2A and subsequent treatment with
perfluorobenzene selectively produced the para-substituted
product 2H in 29% isolated yield. Upon further optimization, we
found that excess perfluorobenzene resulted in higher conversion
to desired product. The best results were achieved with DME and
2 equivalents of KHMDS, resulting in 74% isolated product
yield. Similar carborane-substituted phenylene molecules have
been investigated for their luminescent properties, but are
typically synthesized via cross coupling procedures that require
multiple reagents such as CuI and Pd(PPh3)2Cl2.15 Overall, we
demonstrate that SNAr methodology can be applied to both
chloro- and fluoro(hetero)aryl substrates, however, in the latter
case a competing reactivity of the fluoride byproduct needs to be
mitigated by the judicious use of the additional reagents and
solvents.
(RCSA) for a Cottrell Scholar Award and the National Institutes
of Health (NIH) for a Maximizing Investigators Research Award
(MIRA, R35GM124746). C.M. thanks the UCLA Department
of Chemistry and Biochemistry's Daniel Kivelson Foundation
for the Undergraduate Summer Research Fellowship in
Chemistry.
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Lastly, the described methods for forming B–C and C–C bonds
in carboranes prompted us to explore whether these methods can
be used in conjunction with each other to achieve the synthesis of
heterofunctionalized clusters. Treatment of methylated carborane
1E with excess 2-fluoropyridine produced product 2I,
demonstrating that both the B- and C- vertex functionalization
methods can be used in a sequential manner. This compound was
isolated in 38% yield. Single crystals of 2I were grown with
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4. Conclusion
We have developed improved B- and C-vertex functionalization
methods that can effectively afford previously inaccessible
carborane derivatives. Specifically, by employing biaryl
phosphine ligands, we have introduced an improved B-vertex
substitution method that increases the rate of Pd-catalyzed
Kumada cross-coupling conditions. Additionally, we have
expanded the scope of C-vertex substitution while circumventing
the requirement for transition metal-catalyzed cross-coupling. By
utilizing the nucleophilic nature of the C-metalated carboranes,
mild conditions can be used to achieve substitutions of
heterocycles on carboranes. These improved methods represent a
robust addition of transformations now available to the
practitioners in boron cluster chemistry.
5. Acknowledgements
A.M.S. thanks the UCLA Department of Chemistry and
Biochemistry for start-up funds, 3M for a Non-Tenured Faculty
Award, the Alfred P. Sloan Foundation for a Fellowship in
Sevryugina, Y.; Julius, R. L.; Hawthorne, M. F. Inorg. Chem.
2010, 49 (22), 10627; (f) Dziedzic, R. M.; Saleh, L. M. A.; Axtell,